The major objective of this research is to elucidate chemical and physical properties of ligand-bridged bimetallic and polymetallic centers in proteins and related model compounds. Attention will focus on diiron oxo proteins hemerythrin (Hr), methane monooxygen- ase (MMO), ribonucleotide reductase (RR) and purple acid phosphatase (PAP) and on the iron storage protein ferritin (Ft). Among the specific aims are to build binuclear iron molecules capable of reversible 02 binding and catalysis of hydrocarbon oxidation by 02, to characterize structurally and spectroscopically and to model the diiron center in MMO's, and to construct new polyiron oxo complexes as ferritin core models. An important goal is to discover fundamental relationships between structure and function. What features of the coordination chemistry of geometrically similar binuclear iron centers promote reversible 02 binding in Hr, reduction of ribo- to deoxyribonucleotides in RR, methane oxidation in MMO, and phosphate ester hydrolysis in PAP? What reactions control the iron oxo oligomerization steps that lead to the assembly of the polyiron core in Ft? The answers to these questions have many health-related implications. RR catalyzes the first committed step in DNA biosynthesis, and agents that inhibit its function have chemotherapeutic potential as antitumor and antiviral drugs. The preparation of new oxygen transport molecules could assist the development of artificial blood substitutes. Understanding how hydrolytic polymerization reactions of iron are controlled could lead to better management of its biological toxicities. The experimental approach involves first the synthesis of model complexes designed to probe structural, magnetic, spectroscopic and, especially, chemical properties of the di- or polynuclear cores at higher resolution than may be possible with the proteins. The design and construction of binucleating ligands is of specific importance in this stage. New complexes are fully characterized by physical measurements including X-ray crystallography, ESR or NMR magnetic resonance, Raman, infrared, UV-vis, and Mossbauer spectroscopy, by magnetic susceptibility measurements, and by their chemical reactions relative to specific protein functions. To facilitate comparative bioinorganic chemistry, parallel studies of selected proteins, specifically MMO and RR, will be carried out, the goals being to provide detailed structural information, to understand cofactor interactions, and to learn how the protein environment modulates the reaction chemistry of the diiron centers. While the focus is primarily on iron, studies of related binuclear copper and manganese complexes will be continued.